The proposed work will investigate several basic aspects of neuron-target cell relations in the central nervous system (CNS). Of special interest are developmental interactions between afferent axons and target cells that determine the mature properties of specific synaptic connections in the auditory system. The seven proposed experiments will make use of the well-characterized avian brain stem auditory system, in particular the neurons of nucleus magnocellularis (NM). The methods to be employed in this work include surgery on young chick embryos, in vitro and in invo preparations of the brain stem, intracellular and extracellular electrophysiology, iontophoretic injection and histochemical staining of horseradish peroxidase, light- and electron-microscopic methods (including morphometry), and pharmacological analysis of synaptic transmission. It has recently been found that an anomalous functional projection from one NM to the contralateral NM can be experimentally induced by early surgical removal of the otocyst. This projection is a major one, providing functional input capable of synaptically driving NM cells on the side of otocyst removal. Further, it appears to form quite early in development. This anamalous projection offers the very unusual opportunity to examine the developmental consequences of "replacing" one type of afferent with a novel afferent input to the same group of target cells. Several aspects of the development of this novel auditory projection will be examined and contrasted with the development of normal cochlear nerve innervation of NM. In particular, questions about the relative influence of afferent axons or target neurons in specifying a particular property (e.g., axonal convergence ratio or neurotransmitter type) or in initiating a given developmental process (e.g., reduction in axonal branching) will be addressed. In addition, the proposed studies may provide an animal model for the central neural effects of congenital sensorineural hearing loss in humans and also permit critical tests of some current hypotheses about lesion-induced reactive synaptogenesis in the CNS.